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Abstract The deposition of abnormal tau protein is characteristic of Alzheimer’s disease (AD) and a class of neurodegenerative diseases called tauopathies. Physiologically, tau maintains an intrinsically disordered structure and plays diverse roles in neurons. Pathologically, tau undergoes abnormal post-translational modifications and forms oligomers or fibrous aggregates in tauopathies. In this review, we briefly introduce several tauopathies and discuss the mechanisms mediating tau aggregation and propagation. We also describe the toxicity of tau pathology. Finally, we explore the early diagnostic biomarkers and treatments targeting tau. Although some encouraging results have been achieved in animal experiments and preclinical studies, there is still no cure for tauopathies. More in-depth basic and clinical research on the pathogenesis of tauopathies is necessary.

Objective The objective of this study was to identify candidate genes that play important roles in skeletal muscle development in ducks. Methods In this study, we investigated the transcriptional sequencing of embryonic pectoral muscles from two specialized lines: Liancheng white ducks (female) and Cherry valley ducks (male) hybrid Line A (LCA) and Line C (LCC) ducks. In addition, prediction of target genes for the differentially expressed mRNAs was conducted and the enriched gene ontology (GO) terms and Kyoto encyclopedia of genes and genomes signaling pathways were further analyzed. Finally, a protein-to-protein interaction network was analyzed by using the target genes to gain insights into their potential functional association. Results A total of 1,428 differentially expressed genes (DEGs) with 762 being up-regulated genes and 666 being down-regulated genes in pectoral muscle of LCA and LCC ducks identified by RNA-seq (p

The present study aims to evaluate the effects of the antibacterial peptide Microcin J25 (ABP MccJ25) on growth performance, intestinal barrier function, antioxidant capacity and ileal microbiota in pigeon squabs. The 80 pairs of American Silver King pigeon parents and 240 healthy day 1 squabs were randomly divided into four groups, including 4 parent pairs and 12 pigeon squabs per group with 5 replicates. Parent pigeons were fed a basal diet (CON) or the addition of 100, 200, 300 mg/kg of ABP MccJ25 (ABP100, ABP200, and ABP300, respectively) for 4 weeks. Results showed that the group ABP200 remarkably reduced the feed conversion ratio and increased average daily gain in pigeon squabs from 7 to 21 d (p

Abstract Previous observational investigations suggest that structural and diffusion imaging-derived phenotypes (IDPs) are associated with major neurodegenerative diseases; however, whether these associations are causal remains largely uncertain. Herein we conducted bidirectional two-sample Mendelian randomization analyses to infer the causal relationships between structural and diffusion IDPs and major neurodegenerative diseases using common genetic variants-single nucleotide polymorphism (SNPs) as instrumental variables. Summary statistics of genome-wide association study (GWAS) for structural and diffusion IDPs were obtained from 33,224 individuals in the UK Biobank cohort. Summary statistics of GWAS for seven major neurodegenerative diseases were obtained from the largest GWAS for each disease to date. The forward MR analyses identified significant or suggestively statistical causal effects of genetically predicted three structural IDPs on Alzheimer’s disease (AD), frontotemporal dementia (FTD), and multiple sclerosis. For example, the reduction in the surface area of the left superior temporal gyrus was associated with a higher risk of AD. The reverse MR analyses identified significantly or suggestively statistical causal effects of genetically predicted AD, Lewy body dementia (LBD), and FTD on nine structural and diffusion IDPs. For example, LBD was associated with increased mean diffusivity in the right superior longitudinal fasciculus and AD was associated with decreased gray matter volume in the right ventral striatum. Our findings might contribute to shedding light on the prediction and therapeutic intervention for the major neurodegenerative diseases at the neuroimaging level.

Clubroot caused by Plasmodiophora brassicae is a devastating disease of Cruciferous crops. Developing cultivars with clubroot resistance (CR) is the most effective control measure. For the two major Brassica vegetable species B. rapa and B. oleracea, several commercial cultivars with unclear CR pedigrees have been intensively used as CR donors in breeding. However, the continuous occurrence of CR-breaking makes the CR pedigree underlying these cultivars one of the breeders' most urgent concerns. The complex intraspecific diversity of these two major Brassica vegetables has also limited the applicability of CR markers in different breeding programs. Here we first traced the pedigree underlying two kinds of CR that have been widely applied in breeding by linkage and introgression analyses based on public resequencing data. In B. rapa, a major locus CRzi8 underlying the CR of the commercial CR donor ‘DegaoCR117’ was identified. CRzi8 was further shown to have been introgressed from turnip (B. rapa ssp. rapifera) and that it carried a potential functional allele of Crr1a. The turnip introgression carried CRbc, sharing the same coding sequence with the CRb that was also identified from chromosome C07 of B. oleracea CR cultivars with different morphotypes. Within natural populations, variation analysis of linkage intervals of CRzi8, PbBa8.1, CRb, and CRbc yielded easily resolved InDel markers (> 20 bp) for these fundamental CR genes. The specificity of these markers was tested in diverse cultivars panels, and each exhibited high reliability in breeding. Our research demonstrates the value of the practice of applying resequencing big data to solve urgent concerns in breeding programs.

A few observational neuroimaging investigations have reported subcortical structural changes in the individuals who recovered from the coronavirus disease‐2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the causal relationships between COVID-19 and longitudinal changes of subcortical structures remain unclear. We performed two-sample Mendelian randomization (MR) analyses to estimate putative causal relationships between three COVID-19 phenotypes (susceptibility, hospitalization, and severity) and longitudinal volumetric changes of seven subcortical structures derived from MRI. Our findings demonstrated that genetic liability to SARS-CoV-2 infection had a great long-term impact on the volumetric reduction of subcortical structures, especially caudate. Our investigation may contribute in part to the understanding of the neural mechanisms underlying COVID-19-related neurological and neuropsychiatric sequelae.

Summary: Physical activity reduces cancer-associated mortality through multiple mechanisms, including tumor immune microenvironment (TIME) reprogramming. However, whether and how physiological interventions promote anti-tumor immunity remain elusive. Here, we report that clinically relevant voluntary exercise promotes muscle-derived extracellular vesicle (EV)-associated miR-29a-3p for tumor extracellular matrix (ECM) inhibition in patients and mouse models, thereby permitting immune cell infiltration and immunotherapy. Mechanistically, an unbiased screening identifies EV-associated miR-29a-3p in response to leisure-time physical activity or voluntary exercise. MiR-29a-3p-containing EVs accumulate in tumors and downregulate collagen composition by targeting COL1A1. Gain- and loss-of-function experiments and cytometry by time of flight (CyTOF) demonstrate that myocyte-secreted miR-29a-3p promotes anti-tumor immunity. Combining immunotherapy with voluntary exercise or miR-29a-3p further enhances anti-tumor efficacy. Clinically, miR-29a-3p correlates with reduced ECM, increased T cell infiltration, and response to immunotherapy. Our work reveals the predictive value of miR-29a-3p for immunotherapy, provides mechanistic insights into exercise-induced anti-cancer immunity, and highlights the potential of voluntary exercise in sensitizing immunotherapy.

Abstract Combination of tumor immunotherapy with photothermal therapy (PTT) is a feasible tactic to overcome the drawback of immunotherapy such as poor immune response. Via triggering the immunogenic cells death (ICD), PTT can stimulate the activity of immune cells, but meanwhile, the level of adenosine is elevated via the CD73-induced decomposition of ATP which is overexpressed accompanying with the PTT process, resulting in negative feedback to impair the immune stimulation. Herein, we developed a novel biomimetic photothermal nanodrug to specifically block CD73 for inhibition of adenosine production and more efficient priming of the suppressive immune microenvironments. The nanodrug, named as AptEM@CBA, is constructed by encapsulation of photothermal agent black phosphorus quantum dots (BPQDs) and selective CD73 inhibitor α, β-Methyleneadenosine 5′-diphosphate (AMPCP) in chitosan nanogels, which are further covered with aptamer AS1411 modified erythrocyte membrane (EM) for biomimetic camouflage. With AS1411 induced active targeting and EM induced long blood circulation time, the enrichment of the nanodrug tumor sites is promoted. The photothermal treatment promotes the maturation of dendritic cells. Meanwhile, the release of AMPCP suppress the adenosine generation via CD73 blockade, alleviating the impairment of adenosine to dendritic cells and suppressing regulatory T cells, synergically stimulate the activity of T cells. The combination of CD73 blockade with PTT, not only suppresses the growth of primary implanted tumors, but also boosts strong antitumor immunity to inhibit the growth of distal tumors, providing good potential for tumor photoimmunotherapy.

Abstract Background Obesity and hypertension are major risk factors for cardiovascular diseases that affect millions of people worldwide. Both conditions are associated with chronic low-grade inflammation, which is mediated by adipokines such as adiponectin. Adiponectin is the most abundant adipokine that has a beneficial impact on metabolic and vascular biology, while high serum concentrations are associated with some syndromes. This “adiponectin paradox” still needs to be clarified in obesity-associated hypertension. The aim of this study was to investigate how adiponectin affects blood pressure, inflammation, and metabolic function in obesity hypertension using a Chinese adult case-control study. Methods A case-control study that had finished recruiting 153 subjects divided as four characteristic groups. Adiponectin serum levels were tested by ELISA in these subjects among these four characteristic Chinese adult physical examination groups. Waist circumference (WC), body mass index (BMI), systolic blood pressure (SB), diastolic blood pressure (DB), and other clinical laboratory data were collected. Analyzation of correlations between the research index and differences between groups was done by SPSS. Results Serum adiponectin levels in the| normal healthy group (NH group) were significantly higher than those in the newly diagnosed untreated just-obesity group (JO group), and negatively correlated with the visceral adiposity index. With multiple linear egression analysis, it was found that, for serum adiponectin, gender, serum albumin (ALB), alanine aminotransferase (ALT) and high-density lipoprotein cholesterol (HDLC) were the significant independent correlates, and for SB, age and HDLC were the significant independent correlates, and for DB, alkaline phosphatase (ALP) was the significant independent correlate. The other variables did not reach significance in the model. Conclusions Our study reveals that adiponectin’s role in obesity-hypertension is multifaceted and is influenced by the systemic metabolic homeostasis signaling axis. In obesity-related hypertension, compensatory effects, adiponectin resistance, and reduced adiponectin clearance from impaired kidneys and liver all contribute to the “adiponectin paradox”.

Abstract As a common musculoskeletal disorder, frozen shoulder is characterized by thickened joint capsule and limited range of motion, affecting 2–5% of the general population and more than 20% of patients with diabetes mellitus. Pathologically, joint capsule fibrosis resulting from fibroblast activation is the key event. The activated fibroblasts are proliferative and contractive, producing excessive collagen. Albeit high prevalence, effective anti-fibrosis modalities, especially fibroblast-targeting therapies, are still lacking. In this study, microRNA-122 was first identified from sequencing data as a potential therapeutic agent to antagonize fibroblast activation. Then, Agomir-122, an analog of microRNA-122, was loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Agomir-122@NP), a carrier with excellent biocompatibility for the agent delivery. Moreover, relying on the homologous targeting effect, we coated Agomir-122@NP with the cell membrane derived from activated fibroblasts (Agomir-122@MNP), with an attempt to inhibit the proliferation, contraction, and collagen production of abnormally activated fibroblasts. After confirming the targeting effect of Agomir-122@MNP on activated fibroblasts in vitro, we proved that Agomir-122@MNP effectively curtailed fibroblasts activation, ameliorated joint capsule fibrosis, and restored range of motion in mouse models both prophylactically and therapeutically. Overall, an effective targeted delivery method was developed with promising translational value against frozen shoulder. Graphical Abstract

High temperature stress is one of the major environmental factors that affect the growth and development of plants. Although WRKY transcription factors play a critical role in stress responses, there are few studies on the regulation of heat stress by WRKY transcription factors, especially in tomato. Here, we identified a group I WRKY transcription factor, SlWRKY3, involved in thermotolerance in tomato. First, SlWRKY3 was induced and upregulated under heat stress. Accordingly, overexpression of SlWRKY3 led to an increase, whereas knock-out of SlWRKY3 resulted in decreased tolerance to heat stress. Overexpression of SlWRKY3 accumulated less reactive oxygen species (ROS), whereas knock-out of SlWRKY3 accumulated more ROS under heat stress. This indicated that SlWRKY3 positively regulates heat stress in tomato. In addition, SlWRKY3 activated the expression of a range of abiotic stress-responsive genes involved in ROS scavenging, such as a SlGRXS1 gene cluster. Further analysis showed that SlWRKY3 can bind to the promoters of the SlGRXS1 gene cluster and activate their expression. Collectively, these results imply that SlWRKY3 is a positive regulator of thermotolerance through direct binding to the promoters of the SlGRXS1 gene cluster and activating their expression and ROS scavenging.

Trichosanthes kirilowii (T. kirilowii) is a valuable plant used for both medicinal and edible purposes. It belongs to the Cucurbitaceae family. However, its phylogenetic position and relatives have been difficult to accurately determine due to the lack of mitochondrial genomic information. This limitation has been an obstacle to the potential applications of T. kirilowii in various fields. To address this issue, Illumina and Nanopore HiFi sequencing were used to assemble the mitogenome of T. kirilowii into two circular molecules with sizes of 245,700 bp and 107,049 bp, forming a unique multi-branched structure. The mitogenome contains 61 genes, including 38 protein-coding genes (PCGs), 20 tRNAs, and three rRNAs. Within the 38 PCGs of the T. kirilowii mitochondrial genome, 518 potential RNA editing sites were identified. The study also revealed the presence of 15 homologous fragments that span both the chloroplast and mitochondrial genomes. The phylogenetic analysis strongly supports that T. kirilowii belongs to the Cucurbitaceae family and is closely related to Luffa. Collinearity analysis of five Cucurbitaceae mitogenomes shows a high degree of structural variability. Interestingly, four genes, namely atp1, ccmFC, ccmFN, and matR, played significant roles in the evolution of T. kirilowii through selection pressure analysis. The comparative analysis of the T. kirilowii mitogenome not only sheds light on its functional and structural features but also provides essential information for genetic studies of the genus of Cucurbitaceae.

ABSTRACT: To investigate the effect of genetic selection on meat quality in ducks, twenty of each fast growth ducks (LCA) and slow growth ducks (LCC) selected from F6 generation of Cherry Valley ducks (♂) x Liancheng white ducks (♀) were analyzed for carcass characteristics, meat quality (physicochemical and textural characteristics), amino acid and fatty acid profiles at 7 wk. Results showed that live body weight, slaughter weight, eviscerated yield and abdominal fat percentage of LCA were significantly higher than those in LCC ducks (P < 0.01). Moreover, the average area and diameter of myofiber were larger in LCA than LCC ducks (P < 0.01). The breast and thigh muscles of LCA exhibited significantly lower water holding capacity and thermal loss compared with LCC ducks (P < 0.01). In addition, the content of nonessential amino acids (Glu, Asp, and Arg) in breast muscles and Asp, Ser, Thr, and Met in thigh muscles was higher in LCC than LCA ducks (P < 0.05). The proportion of polyunsaturated fatty acids (PUFA) in breast muscles of LCC was higher than LCA ducks (P < 0.05). However, the content of saturated fatty acids (SFA) in breast and thigh muscles of LCA was higher compared with LCC ducks (P < 0.05). The proportion of monounsaturated fatty acids (MUFA) in thigh muscles was significantly higher in LCC compared with LCA ducks (P < 0.01). Finally, multiple traits were evaluated by applying principal component analysis (PCA) and the results indicated that PUFA and SFA in breast muscles of LCA played important roles in meat quality, followed by Warner-Bratzler shear force (WBSF) and MUFA. However, water holding capacity (WHC) had a dominant effect in meat quality of thigh muscles in both LCA and LCC ducks.

This study aimed to uncover the trend of mental health in China over the years and the influence of related social factors. This study employed a cross-temporal meta-analysis (CTMA). The study analyzed 182 studies from 1993 to 2017. A total of 83,603 participants were included in 182 studies. Symptom Checklist-90 (SCL-90) Scale. From 1993 to 2001 and from 2004 to 2017, the scores for each dimension for mental health of older adults were relatively stable, and the absolute value of the effect size was between 0.02 and 0.62. From 2001 to 2003 and from 2003 to 2004, the scores of each dimension of older adults changed greatly. From 2001 to 2003, the total mean score of SCL-90 and the scores of different dimensions in older adults showed a rapidly decreasing trend, with the d ranging from −0.40 to −0.93. From 2003 to 2004, the scores of all dimensions in SCL-90 showed a trend of sharp increase, and the d of each dimension was 0.40 to 0.89. The mental health status of the older adults is declining as a whole and has a large fluctuation from 2001 to 2004 various social development indicators, including Gross Domestic Product (GDP), per capita, divorce rate, unemployment rate, and Engel’s coefficient, demonstrated a significant correlation with mental health status

Abstract Fiber‐reinforced hydrogel composites are widely employed in many engineering applications, such as drug release, and flexible electronics, with more flexible mechanical properties than pure hydrogel materials. Comparing to the hydrogel strengthened by continuous fiber, the meta‐fiber reinforced hydrogel provides stronger individualized design ability of deformation patterns and tunable stiffness, especially for the elaborate applications in joint, cartilage, and organ. In this paper, a novel structure design strategy based on deep learning algorithm is proposed for hydrogel reinforced by meta‐fiber to achieve targeted mechanical properties, such as stress and displacement fields. A solid mechanic model for meta‐fiber reinforced hydrogel is first developed to construct the dataset of fiber distribution and the corresponding mechanical properties of the composite. Generative adversarial network (GAN) is then trained to characterize the relationship between stress or displacement field, and meta‐fiber distribution. The well‐trained GAN is implemented to design meta‐fiber reinforced hydrogel composite structure under specific operation conditions. The results show that the deep learning method may efficiently predict the structure of the hydrogel composite with satisfied confidence, and has great potential for applications in drug delivery and flexible electronics.

Summary: Constructing platinum-like materials with excellent catalytic activity and low cost has great significance for hydrogen evolution reaction (HER) during electrolysis of water. Herein, palladium nanoparticles (NPs) deposition on the surface of Co NPs using nitrogen-doped carbon (NC) as substrate, denoted as N-ZIFC/CoPd-30, are manufactured and served as HER electrocatalysts. Characterization results and density functional theory calculations validate that Pd-Co heterojunctions with NC acting as “electron donators” promote the Pd species transiting to the electron-rich state based on an efficient electron transfer mechanism, namely the N-C polar bonds induced strong metal-support interaction effect. The electron-rich Pd sites are beneficial to HER. Satisfactorily, N-ZIFC/CoPd-30 have only low overpotentials of 16, 162, and 13 mV@-10 mA cm−2 with the small Tafel slopes of 98 mV/decade, 126 mV/decade, and 72 mV/decade in pH of 13, 7, and 0, respectively. The success in fabricating N-ZIFC/CoPd opens a promising path to constructing other platinum-like electrocatalysts with high HER activity.

Abstract Inquiry-based science teaching has emerged as a prominent trend in science education. Nevertheless, it remains uncertain how teachers' self-efficacy in regard to the teaching of science as inquiry (TSI) affects students' science learning, especially considering the scarcity of research on its impact on students' Science Process Skills (SPSs). To investigate the impact of teachers' TSI on students' SPSs, this study conducted a questionnaire survey involving 539 eighth-grade students and 75 teachers from 7 junior high schools. Our Multilevel Model analysis results revealed a positive correlation between students' creative tendencies and SPSs. The results of the Cross-Level Moderation Models indicated that TSI moderated the relationship between students' creative tendencies and their SPSs, with this relationship strengthening as TSI increased. These study findings carry significant implications for both inquiry-based science education and teacher education.

【Objective】A joint evaluation on Ricinus communis cross combinations was conducted to provide a theoretical reference for screening high-yield varieties suitable for mechanical harvest.【Method】The yield trait, adaptability for mechanical harvest and photosynthetic performance of 30 R. communis cross combinations were jointly evaluated by grey relational analysis, principal component analysis and cluster analysis.【Result】In the grey relational analysis, 6 combinations including N19 (0.768), N7 (0.751), N11 (0.727), N10 (0.717), N6 (0.713) and N13 (0.712) with weighted correlation degree between various combinations and the ideal varieties were screened out. Among which, the former 4 combinaitons had higher weighted correlation degrees than that in Zibi 5 (0.714), and the weighted correlation degrees of the latter 2 were close to that in Zibi 5. Principal analysis results showed that, 10 traits were classified into 3 principal components, namely, plant type factor, yield determining factor and photosynthetic and branching angle factor, with a cumulative contribution rate of 67.07%. Among the 30 combinations, the comprehensive scores of 21 combinations were higher than that of Zibi 5 (-0.699), and only 4 combinations, N18 (2.370), N4 (1.848), N19 (1.742) and N11 (1.019) had comprehensive scores larger than 1, of which N19 was the most prominent with a much higher score than that in other 3 combinations. Cluster analysis revealed that, the 30 combinations could be classified into 4 groups at Euclidean distance value equal to 22. Among them, Group IV members (including N19, N11 and N30) with the best overall performance was most similar to the ideal varieties based on the average performance in each cluster, however, the branching angle (59.10°) was large and still expected to be improved.【Conclusion】Based on the above 3 evaluation results, the comprehensive evaluation avoids the acceptance of redundant germplasm and the loss of elite germplasm. The N19 and N11 with high yield, good plant type and high photosynthetic rate were selected as the optimal Ricinus communis cross combinations, and their comprehensive performances were better than that of Zibi 5, providing a direction for further improvement of varieties.out of varieties.

Abstract The selective oxidative dehydrogenation of ethane (ODHE) is attracting increasing attention as a method for ethylene production. Typically, thermocatalysts operating at high temperatures are needed for C–H activation in ethane. In this study, we describe a low temperature (

Abstract Background Lateral wall fractures represent crucial risk factors for postoperative internal fixation failure in intertrochanteric femoral fractures. However, no consensus exists on the type of lateral wall fracture requiring interventional management. This study aimed to investigate the effect of residual lateral wall volume on the postoperative stability of intertrochanteric femur fractures with associated lateral wall fractures, providing valuable reference for the clinical management of the lateral wall. Methods Eleven bone defect models of intertrochanteric femur fractures with varying residual lateral wall volumes were constructed using finite element analysis. These models were fixed with proximal femoral nail antirotation (PFNA). Simulations of von Mises stress and displacement distribution of the PFNA and femur during normal walking were conducted. Statistical analysis was performed to assess the correlation between volume and the maximum von Mises stresses and displacements of the PFNA and femur. Results In all 11 models, the maximum von Mises stress and displacement of the helical blade, intramedullary nail, and femur occurred at the same locations. As residual lateral wall volume increased, the maximum von Mises stress and displacement of the helical blade, intramedullary nail, and maximum femoral displacement gradually decreased. However, the overall trend of the maximum femoral von Mises stress gradually decreased. At 70% retention of the residual lateral wall volume, there was a more pronounced change in the value of the maximum stress change of the helical blade and the intramedullary nail. Statistical analysis, including the Shapiro–Wilk test and Pearson correlation analysis, demonstrated a significant negative correlation between volume and the maximum von Mises stress and displacement of the helical blade, intramedullary nail, and femur. Linear regression analysis further confirmed this significant negative correlation. Conclusion Finite element analysis of the residual lateral wall revealed a significant correlation between volume and the postoperative stability of intertrochanteric femur fractures. A volume of 70% may serve as the threshold for stabilizing the residual lateral wall. Volume emerges as a novel index for evaluating the strength of the residual lateral walls.

Terahertz spectroscopy systems, which integrate terahertz sources and detectors, have important applications in many fields such as materials science and security checking. Based on highly sensitive frequency up-conversion detection, large dynamic range spectral measurements in a terahertz region are reported. Our system realized the detection sensitivity at a 10 aJ level with a 2-(3-(4-hydroxystyryl)-5,5-dime-thylcyclohex-2-enylidene) malononitrile (OH1) crystal and a dynamic range up to seven orders. Based on this system, we verified the validity of the spectral measurement with tests which were conducted on monohydrate glucose, anhydrous glucose and mixed tablet samples with a thickness of 0.8 mm in 1~3 THz, respectively. Also, a mini coppery elbow tube with an inner diameter of 1 mm was used for the transmission of a terahertz wave to simulate some strip biological tissue samples. By allowing terahertz to transmit through this tube filled with 0.5 g glucose powder, we successfully obtained the absorption spectrum with a minimum transmittance at the absorption peak in the order of 10−4.

Sepia pharaonis, commonly known as the pharaoh cuttlefish, is a valued cephalopod in aquaculture. However, its sensitivity to salinity fluctuations has constrained its cultivation, especially in regions with varying salinity and during rainy seasons. To address this, our study implemented a graded salinity reduction approach, enabling S. pharaonis to acclimate to an environment with a salinity of 20. Despite a reduction in growth parameters such as mantle length and body weight in the Low-Salinity Acclimation group (LSA), the survival rates were largely consistent with the control group. After the acclimation process, the LSA group demonstrated a strikingly high survival rate of nearly 100% in salinity ranges from 18 to 24, a span previously thought to be deadly for non-acclimated S. pharaonis. Our evaluations indicate that the serum osmotic pressure and ion concentration of S. pharaonis decline with decreasing seawater salinity. During this process, there were significant alterations in the Na+/K+-ATPase activity and the content of free amino acids, suggesting their crucial role in low-salt osmoregulation. Overall, this study not only highlights the potential of the graded salinity reduction method to enhance the adaptability of S. pharaonis to fluctuating salinities, but also underscores the potential of graded salinity reduction as an innovative approach to enhance the resilience of aquaculture species.

The Middle Permian Qixia Formation in the Shuangyushi area, northwestern Sichuan Basin, develops shoal-facies dolomite reservoirs. To pinpoint promising reservoirs in the Qixia Formation, deep thin shoal-facies dolomite reservoirs were predicted using the techniques of pre-stack Kirchhoff-Q compensation for absorption, inverse Q filtering, low-to high-frequency compensation, forward modeling, and facies-controlled seismic meme inversion. The results are obtained in six aspects. First, the dolomite reservoirs mainly exist in the middle and lower parts of the second member of Qixia Formation (Qi2 Member), which coincide with the zones shoal cores are developed. Second, the forward modeling shows that the trough energy at the top and bottom of shoal core increases with increasing shoal-core thickness, and weak peak reflections are associated in the middle of shoal core. Third, five types of seismic waveform are identified through waveform analysis of seismic facies. Type-I and Type-II waveforms correspond to promising facies (shoal core microfacies). Fourth, vertically, two packages of thin dolomite reservoirs turn up in the sedimentary cycle of intraplatform shoal in the Qi2 Member, and the lower package is superior to the upper package in dolomite thickness, scale and lateral connectivity. Fifth, in plane, significantly controlled by sedimentary facies, dolomite reservoirs laterally distribute with consistent thickness in shoal cores at topographical highs and extend toward the break. Sixth, the promising prospects are the zones with thick dolomite reservoirs and superimposition of horst–graben structural traps.

Background: Sarcopenia is characterized by decreased muscle mass and strength, posing threat to quality of life. Air pollutants are increasingly recognized as risk factors for diseases, while the relationship between the two remains to be elucidated. This study investigated whether exposure to ambient air pollution contributes to the development of sarcopenia. Methods: We employed the data from the UK Biobank with 303,031 eligible participants. Concentrations of PM2·5, NO2, and NOx were estimated. Cox proportional hazard regression models were applied to investigate the associations between pollutants and sarcopenia. Results: 30,766 probable sarcopenia cases was identified during the follow-up. We observed that exposure to PM2.5 (HR, 1.232; 95% CI, 1.053–1.440), NO2 (HR, 1.055; 95% CI, 1.032–1.078) and NOx (HR, 1.016; 95% CI, 1.007–1.026) were all significantly associated with increased risk for probable sarcopenia for each 10 μg/m3 increase in pollutant concentration. In comparison with individuals in the lowest quartiles of exposure, those in the upper quartiles had significantly increased risk of probable sarcopenia. Sarcopenia-related factors, e.g., reduced lean muscle mass, diminished walking pace, and elevated muscle fat infiltration ratio, also exhibited positive associations with exposure to ambient air pollution. On the contrary, high level physical activity significantly mitigated the influence of air pollutants on the development of probable sarcopenia. Conclusions: Air pollution exposure elevated the risk of developing sarcopenia and related manifestations in a dose-dependent manner, while physical activity maintained protective under this circumstance. Efforts should be made to control air pollution and emphasize the importance of physical activity for skeletal muscle health under this circumstance.

Brain network analysis provides essential insights into the diagnosis of brain disease. Integrating multiple neuroimaging modalities has been demonstrated to be more effective than using a single modality for brain network analysis. However, a majority of existing brain network analysis methods based on multiple modalities often overlook both complementary information and unique characteristics from various modalities. To tackle this issue, we propose the Beta-Informativeness-Diffusion Multilayer Graph Embedding (BID-MGE) method. The proposed method seamlessly integrates structural connectivity (SC) and functional connectivity (FC) to learn more comprehensive information for diagnosing neuropsychiatric disorders. Specifically, a novel beta distribution mapping function (beta mapping) is utilized to increase vital information and weaken insignificant connections. The refined information helps the diffusion process concentrate on crucial brain regions to capture more discriminative features. To maximize the preservation of the unique characteristics of each modality, we design an optimal scale multilayer brain network, the inter-layer connections of which depend on node informativeness. Then, a multilayer informativeness diffusion is proposed to capture complementary information and unique characteristics from various modalities and generate node representations by incorporating the features of each node with those of their connected nodes. Finally, the node representations are reconfigured using principal component analysis (PCA), and cosine distances are calculated with reference to multiple templates for statistical analysis and classification. We implement the proposed method for brain network analysis of neuropsychiatric disorders. The results indicate that our method effectively identifies crucial brain regions associated with diseases, providing valuable insights into the pathology of the disease, and surpasses other advanced methods in classification performance.

A subset of patients experiences persistent fatigue symptoms after COVID-19, and patients may develop long COVID, which is characterized by lasting systemic symptoms. No treatments for this condition have been validated and are urgently warranted. In this pilot study, we assessed whether treatment with low-dose naltrexone (LDN, 4.5 mg/day) and supplementation with NAD + through iontophoresis patches could improve fatigue symptoms and quality of life in 36 patients with persistent moderate/severe fatigue after COVID-19. We detected a significant increase from baseline in SF-36 survey scores after 12 weeks of treatment (mean total SF-36 score 36.5 [SD: 15.6] vs. 52.1 [24.8]; p

Given the growing incidence rates of suicide among college students and the potential lifelong consequences of suicide, it is imperative to better understand the factors that reduce the rates at which college students in a clinical sample engage in suicide. This study examines the relationship between social exclusion and suicide intention, the mediating effect of depression, and the moderating effect of meaning in life. Two hundred and ninety-nine Chinese college students, aged from 18 to 22 years (56.86% female, M age = 20.14, SD = 1.27) completed questionnaires assessing their social exclusion, suicide intention, depression, and meaning in life. The result revealed that social exclusion was positively associated with suicide intention, and depression mediated this relationship. In addition, this mediating effect of depression was moderated by meaning in life. That is, the mediation effect was stronger for students with a higher level of meaning in life. These findings provide educational suggestions for preventing and intervening in suicide intention among college students.

Abstract Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane protein that is predominantly expressed by microglia in the brain. The proteolytic shedding of TREM2 results in the release of soluble TREM2 (sTREM2), which is increased in the cerebrospinal fluid of patients with Alzheimer’s disease (AD). It remains unknown whether sTREM2 regulates the pathogenesis of AD. Here we identified transgelin-2 (TG2) expressed on neurons as the receptor for sTREM2. The microglia-derived sTREM2 binds to TG2, induces RhoA phosphorylation at S188, and deactivates the RhoA-ROCK-GSK3β pathway, ameliorating tau phosphorylation. The sTREM2 (77-89) fragment, which is the minimal active sequence of sTREM2 to activate TG2, mimics the inhibitory effect of sTREM2 on tau phosphorylation. Overexpression of sTREM2 or administration of the active peptide rescues tau pathology and behavioral defects in the tau P301S transgenic mice. Together, these findings demonstrate that the sTREM2-TG2 interaction mediates the cross-talk between microglia and neurons. sTREM2 and its active peptide may be a potential therapeutic intervention for tauopathies including AD.

Probabilistic damage tolerance is a critical method to understand and communicate risk and safety. This paper reviews recent research on the probabilistic damage tolerance design for life-limited parts. The vision of the probabilistic damage tolerance assessment is provided. Five core parts of the probabilistic damage tolerance method are introduced separately, including the anomaly distribution, stress processing and zone definition, fatigue and fracture calculation method, probability of failure (POF) calculation method, and the combination with residual stress induced by the manufacturing process. The above currently-available risk assessment methods provide practical tools for failure risk predictions and are applied by the airworthiness regulations. However, new problems are exposed with the development of the aero-engines. The time-consuming anomaly distribution derivation process restricts the development of the anomaly distribution, especially for the developing aviation industries with little empirical data. Additionally, the strong transient characteristic is prominent because of the significant temperature differences during the take-off and climbing periods. The complex loads then challenge the fatigue and fracture calculation model. Besides, high computational efficiency is required because various variables are considered to calculate the POF. Therefore, new technologies for the probabilistic damage tolerance assessment are provided, including the efficient anomaly distribution acquisition method based on small samples, the zone definition method considering transient process, and stress intensity factor (SIF) solutions under arbitrary stress distributions combined with the machine learning method. Then, an efficient numerical integration method for calculating failure risk based on the probability density evolution theory is proposed. Meanwhile, the influence of the manufacturing process on residual stress and the failure risk of the rotors is explored. The development of the probabilistic damage tolerance method can meet the requirement of the published airworthiness regulation Federal Aviation Regulation (FAR) 33.70 and guide the modification or amendment of new regulations to ensure the safety of the high-energy rotors.

Objective: To understand the prevalence of home-related anxiety among adolescent athletes during the novel coronavirus pandemic and to ascertain the factors influencing this anxiety. Methods: We employed cluster sampling to select 1150 adolescent athletes (aged 8–18 years) from six sports training schools in Yantai City, Shandong Province. Mental health status was assessed and recorded. Chi-square tests and multivariable logistic regression were used to analyze the factors contributing to athletes’ anxiety. Results: The survey revealed a COVID-19 infection rate of 38.23% (437 individuals) with an anxiety score of 40.98 ± 8.20 and an anxiety detection rate of 11.29% (129 individuals) during the COVID-19 epidemic. Female athletes exhibited a higher anxiety rate of 14.40% compared to 8.40% in male athletes. Multivariate analysis identified female gender as a risk factor for anxiety (OR = 1.64), while participation in aquatics emerged as a protective factor (OR = 0.24, 95% CI: 1.08–2.48). Professional training duration exceeding three years increased anxiety risk (OR = 3.05, 95% CI: 1.67–5.58), as did not seeking help during difficulties (OR = 2.59, 95% CI: 1.33–5.01). Interestingly, parental care was linked to increased anxiety risk (OR = 2.44, 95% CI 1.34–4.44), while care from friends was protective (OR = 0.60, 95% CI: 0.36–1.01), which was possibly due to the pressure associated with parental expectations. Conclusions: Adolescent athletes, particularly females and those with extended training durations, exhibit a heightened susceptibility to anxiety. This study also highlights that athletes who proactively seek assistance during challenging situations tend to experience lower anxiety levels. Additionally, a lack of COVID-19 infection and the involvement of concerned parents contribute to reduced anxiety among these young athletes.

As an important part of head protection equipment, research on the material and structural application of helmet liners has always been one of the hotspots in the field of helmets. This paper first discusses common helmet liner materials, including traditional polystyrene, polyethylene, polypropylene, etc., as well as newly emerging anisotropic materials, polymer nanocomposites, etc. Secondly, the design concept of the helmet liner structure is discussed, including the use of a multi-layer structure, the addition of geometric irregular bubbles to enhance the energy absorption effect, and the introduction of new manufacturing processes, such as additive manufacturing technology, to realize the preparation of complex structures. Then, the application of biomimetic structures to helmet liner design is analyzed, such as the design of helmet liner structures with more energy absorption properties based on biological tissue structures. On this basis, we propose extending the concept of bionic structural design to the fusion of plant stalks and animal skeletal structures, and combining additive manufacturing technology to significantly reduce energy loss during elastic yield energy absorption, thus developing a reusable helmet that provides a research direction for future helmet liner materials and structural applications.

Abstract Congenital anomalies of the kidney and urinary tract (CAKUT) are disorders resulting from defects in the development of the kidneys and their outflow tract. Copy number variations (CNVs) have been identified as important genetic variations leading to CAKUT, whereas most CAKUT-associated CNVs cannot be attributed to a specific pathogenic gene. Here we construct coexpression networks involving long noncoding RNAs (lncRNAs) within these CNVs (CNV-lncRNAs) using human kidney developmental transcriptomic data. The results show that CNV-lncRNAs encompassed in recurrent CAKUT associated CNVs have highly correlated expression with CAKUT genes in the developing kidneys. The regulatory effects of two hub CNV-lncRNAs (HSALNG0134318 in 22q11.2 and HSALNG0115943 in 17q12) in the module most significantly enriched in known CAKUT genes (CAKUT_sig1, P = 1.150 × 10−6) are validated experimentally. Our results indicate that the reduction of CNV-lncRNAs can downregulate CAKUT genes as predicted by our computational analyses. Furthermore, knockdown of HSALNG0134318 would downregulate HSALNG0115943 and affect kidney development related pathways. The results also indicate that the CAKUT_sig1 module has function significance involving multi-organ development. Overall, our findings suggest that CNV-lncRNAs play roles in regulating CAKUT genes, and the etiologies of CAKUT-associated CNVs should take account of effects on the noncoding genome.

Abstract Background Data on the impact of age at onset of overweight/obesity on the risk of hypertension are limited. We aimed to investigate the above-mentioned association in Chinese population. Methods 6700 adults who participated in at least three survey waves and were free of overweight/obesity and hypertension on first survey were included using China Health and Nutrition Survey. The age of participants at the onset of overweight/obesity (body mass index ≥ 24 kg/m2) and subsequent hypertension occurrence (blood pressure ≥ 140/90 mmHg or use of antihypertensive medication) were identified. We used the covariate-adjusted Poisson model with robust standard error to calculate the relative risk (RR) and 95% confidence interval (95%CI) to examine the relationship between the age at onset of overweight/obesity and hypertension. Results There were 2,284 new-onset overweight/obesity cases and 2,268 incident cases of hypertension during an average 13.8-year follow-up period. Compared with the population without overweight/obesity, the RR (95% CI) of hypertension was 1.45 (1.28–1.65), 1.35 (1.21–1.52) and 1.16 (1.06–1.28) for overweight/obesity onset in participants aged

An investigation was performed to evaluate the effect of vanadium (V) addition on the microstructure and the tensile behavior of Fe–27Mn–8Al-1.0C austenite lightweight steel after annealing and subsequently aging. The grain size of austenite in V-added steels was effectively refined and many nano-sized VC particles were observed in the austenite grains, compared to V-free steels, under annealed conditions. Subsequent aging promotes the precipitation of κ-carbide from the austenite matrix, and the dual-nanoprecipitation consisting of nano-sized VC and κ-carbide particles further improves the strength of the steel. Because of this, the current steels have good ductility (up to 41% total elongation) even when aged and high yield and ultimate tensile strengths of up to 1009 MPa and 1243 MPa, respectively. By examining the dislocation structure of the specimens during deformation, it was also possible to determine how precipitates affected the rate of strain hardening. As a result, the strain hardening rate of the V-added steel after aging is effectively improved at the initial deformation by the precipitation of VC particles, which compensates for the decrease in strain hardening rate due to shearable κ-carbide. This study provides a strategy to obtain an excellent combination of strength and ductility in lightweight steel by V microalloying and simple thermomechanical treatment.

Abstract Background The occurrence of a diabetic foot ulcer (DFU) is a significant complication of diabetes that often precedes the need for amputation. Autologous platelet-rich plasma (Au-PRP), a substance abundant in various growth factors and cytokines, is increasingly being recognized as a promising method for promoting ulcer healing due to its potential similarities to the physiological wound healing process. Methods The databases Medline, EMBASE, PubMed, and the Cochrane Library were systematically accessed on January 26, 2023, without any consideration for the date of publication. The selection and assessment of research studies were conducted autonomously, based on predetermined criteria and methodological standards. Two researchers gathered data and evaluated the potential for bias separately. We utilize the Stata 17.0 software to conduct data analysis and generate relevant visual representations. Results The results of the meta-analysis indicate that autologous PRP has a significant positive effect on the healing rate (RR = 1.42, 95% CI 1.30–1.56, P 0.05) when compared to conventional therapy. Conclusions Au-PRP therapy has been shown to facilitate the process of wound healing and represents a viable and secure therapeutic alternative for individuals with DFU.

The satellite galaxy Crater II of the Milky Way is extremely cold and exceptionally diffuse. These unusual properties are challenging to understand in the standard model of cold dark matter. We use controlled N -body simulations to investigate the formation of Crater II in self-interacting dark matter (SIDM), where dark matter particles can scatter and thermalize. Taking the orbit motivated by the measurements from Gaia Early Data Release 3, we show a strong self-interacting cross section per particle mass of 60 cm ^2 g ^−1 is favored for Crater II. The simulated SIDM halo, with a 1 kpc core, leads to both a low stellar velocity dispersion and a large half-light radius for Crater II. These characteristics remain robust regardless of the initial stellar distribution.

In two Baijiu-making distilleries, multiple batches of Nongxiangxing Baijiu were produced from four varieties of brewing sorghum. Using high performance gas chromatography, the flavor compounds in Baijiu samples were detected, and differences in their composition and influencing factors were investigated. It was found that distillery, brewing batch, and sorghum variety all affected the composition of flavor compounds, where brewing batch had a greater influence than sorghum variety. With respect to Baijiu samples of different varieties of sorghum, the types and quantities of differential flavor compounds varied greatly with distilleries and brewing batches, and six reliable differential flavor compounds were obtained, including 2-methyl-1-butanol, sec-butyl alcohol, isobutanol, isoamyl alcohol, methanol, and propionic acid. The fusel oil content in Baijiu sample produced by northern hybrid japonica sorghum was significantly higher than that in glutinous sorghums (Jinuoliang No.1 and Jinuoliang No.2). The acidity of Jiupei at the beginning of brewing significantly affected the composition of flavor compounds, the amount of esters and aldehydes, and the content of propionic acid and methanol in Baijiu sample (P

The Tibetan Plateau underwent rapid uplift and complex lithospheric modification during the Cenozoic under the continuing collision and subduction of the Indian Plate, but the present-day vertical dynamic motion and crustal deformation of the plateau remain controversial. This paper calculates the flexural isostatic gravity anomalies on the Tibetan Plateau and its neighboring blocks based on the flexural model with variable effective elastic thickness and using topographic data and Earth's gravity field model. The results show that the isostatic gravity anomalies on the Tibetan Plateau range from -120 to 90 mGal, with the central part characterized by distinct positive anomalies and the margins by significant negative anomalies. Minimal values occur in the northwest Tibetan Plateau and its adjacent Pamir Plateau, while maximal values occur in the northwest part of the Himalaya block. In addition, to the north and east of the Tibetan Plateau, the Tarim Basin and Sichuan Basin show large areas of positive isostatic anomalies. These features suggest that the crust of the Tibetan Plateau and its surroundings is now in a nonisostatic state, with the overall uplift of the older block under the effect of plate collision and compression, leading to positive isostatic anomalies. In younger orogenic regions, crustal deformation is primarily characterized by surface uplift and strong thickening of the lower crust, resulting in negative isostatic anomalies. In the central and northern parts of the plateau, the direction of isostatic adjustment is consistent with the trend of crustal vertical motion. However, south and east of the plateau (e.g., the Himalaya block and Sichuan Basin), the direction of isostatic adjustment is opposite to that observed for surface deformation. This suggests that the Indian Plate collision and subduction still control the crustal deformation processes in the southern and eastern parts of the Tibetan Plateau and its neighboring blocks. However, further north, the crust regains an isostatic state through isostatic adjustment.

A transcriptomic analysis of lncRNAs within copy-number variations identifies HSALNG0104472 as a potential lncRNA effector of cardiac defects in non-syndromic congenital heart disease.

In order to study the optimal extraction process of antioxidants from Malus hupehensis leaves, hydroxyl radical scavenging rate was taken as a reference index, and the extraction conditions of antioxidants from Malus hupehensis leaves was studied by response surface optimization ultrasonic-assisted enzymatic method. The results showed that the best process of ultrasonic-assisted enzyme method was 100 W ultrasonic power, liquid to material ratio 17:1 mL∙g−1, ultrasonic time 32 min, cellulase addition 2.6%, enzymatic digestion time 49 min. The hydroxyl radical scavenging rate was 89.9%±0.06% under this condition, the flavonoid content in the extract was 14.01%, the polyphenol content was 8.93%, and the polysaccharide content was 7.65%, compared with the decoction method, reflux method, enzymatic method and ultrasonic method, the active substance content was increased by more than 10%, the DPPH scavenging rate and hydroxyl radical scavenging rate were increased by more than 20%. It's better to extraction of antioxidants from Malus hupehensis leaves by ultrasonic aided enzymatic method.

The catalytic partial oxidation of methane (CPOM) to methanol has been regarded as a promising approach for methane utilization, despite that the conversion remains a formidable challenge in the perspective of catalysts. A novel catalyst system of multi-wall carbon nanotubes (MWCNTs) that supported Fe2O3 with existing I2, consisting of non-noble metal and working in weak acid at an ambient temperature, was investigated for CPOM. MWCNTs supported the Fe2O3 catalyst, which was prepared by the impregnation method and characterized via HRTEM, XRD, XPS, FT-IR, and BET techniques. The characterization results reveal that, as a non-noble metal catalyst, the Fe2O3/MWCNTs catalyst had a good catalytic performance and stability in the CPOM. With the variation of reaction pressure and the dosage of Fe2O3/MWCNTs, the catalyst system obtained the highest methane conversion rate of 7.41% and methanol selectivity of 86.3%, which is analogous to that of the equivalently strong acid catalyst system. The I2-Fe2O3/MWCNTs catalyst system has great potential in the application of CPOM under mild, environmentally benign conditions, such as non-noble metal requirement, ambient temperature, and weak acid. The reaction mechanism was discussed.

Forest plants contain abundant natural products, providing a valuable resource for obtaining compounds with various functional activities, such as antimicrobial, lipid-lowering, and immunoregulatory activities. The development of efficient tools for rapidly screening functional natural products from forest plants is essential for human health. In this study, we constructed some transgenic strains (Escherichia coli) containing Ahy1-1 riboswitches that respond to cyclic di-guanylate (c-di-GMP), serving as a novel bacteriostatic target. The Ahy1-1 riboswitches contained the LacZ gene (encoding β-galactosidase) and c-di-GMP aptamer in order to monitor β-galactosidase activity due to changes in c-di-GMP. After co-incubating with extracts from fresh orange peel, fresh tea leaves, and Fuzhuan brick tea, the orange peel exhibited a significant inhibition of c-di-GMP generation. The extract of tea leaves had a minor influence on the synthesis of c-di-GMP, whereas Fuzhuan brick tea, which is fermented by various microorganisms, inhibited the production of c-di-GMP. Our constructed transgenic strains could be used to screen for antibacterial agents from forest plants. Beyond antibacterial agents, other functional compounds from forest plants could be selected by designing diverse riboswitches.

BackgroundThe neutrophil-to-lymphocyte ratio (NLR) is a marker of inflammation that can be obtained quickly, conveniently, and cheaply from blood samples. However, there is no research to explore the effects of sex and age on the relationship between the NLR and mild cognitive impairment (MCI) in community-dwelling older adults.MethodsA total of 3,169 individuals aged over 60 years in Shanghai were recruited for face-to-face interviews, and blood samples were collected. MCI was assessed by the Mini-Mental State Examination (MMSE) and the Instrumental Activities of Daily Living (IADL) scale, and neutrophil count and lymphocyte counts were measured in fasting blood samples. The NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count.ResultsIn females, the NLR in the MCI group was significantly higher than that in the cognitively normal group (2.13 ± 0.94 vs. 1.85 ± 0.83, p

The dauer larva is a specialized stage of worm development optimized for survival under harsh conditions that have been used as a model for stress resistance, metabolic adaptations, and longevity. Recent findings suggest that the dauer larva of Caenorhabditis elegans may utilize external ethanol as an energy source to extend their lifespan. It was shown that while ethanol may serve as an effectively infinite source of energy, some toxic compounds accumulating as byproducts of its metabolism may lead to the damage of mitochondria and thus limit the lifespan of larvae. A minimal mathematical model was proposed to explain the connection between the lifespan of a dauer larva and its ethanol metabolism. To explore theoretically if it is possible to extend even further the lifespan of dauer larvae, we incorporated two natural mechanisms describing the recovery of damaged mitochondria and elimination of toxic compounds, which were previously omitted in the model. Numerical simulations of the revised model suggested that while the ethanol concentration is constant, the lifespan still stays limited. However, if ethanol is supplied periodically, with a suitable frequency and amplitude, the dauer could survive as long as we observe the system. Analytical methods further help to explain how feeding frequency and amplitude affect lifespan extension. Based on the comparison of the model with experimental data for fixed ethanol concentration, we proposed the range of feeding protocols that could lead to even longer dauer survival and it can be tested experimentally.

Severe deformation of surrounding rock and excess-gas are the main problems faced in mining of high-gas coal seam. This paper analyzes the deformation characteristics and mechanical model of surrounding rock in high-gas coal seam, and proposes the control technology of surrounding rock deformation and gas prevention and control. Based on this, the entry automatically formed by roof cutting (EAFRC) surrounding rock control technology and constant resistance large deformation anchor cable (CRLDA) support control technology in Shaqu coal mine are put forward. At the same time, the surrounding rock stress and gas migration law of the working face under traditional mining method and EAFRC mining were compared and analyzed. Through the field engineering test, the monitoring and analysis of surrounding rock deformation and gas concentration, the average surrounding rock deformation of roof cutting roadway is 310 mm, and the gas concentration of retained roadway by roof cutting is 0.31%. Through the research in this paper, the surrounding rock stability and gas control of the working face have been realized, and the non-pillar mining of EAFRC has ensured the safe mining of high gas working faces, which provides a reference for the mining of similar mines in non-pillar mining. At the same time, the technical system of EAFRC in non-pillar mining was established, which promoted the development and application of non-pillar mining.

Abstract Background Pneumocystis jirovecii pneumonia (PJP) is a life-threatening disease with increasing prevalence in patients with rheumatic disease. Trimethoprim/sulfamethoxazole (TMP/SMX) is an effective treatment for patients with rheumatic disease hospitalized for PJP. This study aimed to describe the 90-day mortality of patients with rheumatic disease complicated by PJP and investigate whether the administration of TMP/SMX after 7 days from initial symptoms correlates with 90-day mortality. Methods We enrolled consecutive patients with rheumatic disease complicated with PJP in our center from August 2018 to August 2021. The participants were classified into two groups according to when TMP/SMX was initiated: early (within the first 7 days) and late (after 7 days). The primary outcome was 90-day PJP-related mortality. Multivariate cox regression and Kaplan–Meier survival analyses were conducted to identify the risk factors for mortality and examine differences in survival between early and late use of TMP/SMX. Results Thirty-seven patients with rheumatic disease (median age 50.1 years, 24.3% male) complicated by PJP were enrolled in our study, and 15 (40.5%) patients died at or before 90 days of follow-up. The most common comorbidity was systemic lupus erythematosus (14, 37.8%), followed by inflammatory myopathy (11, 27.9%). Patients in the early group were less likely to require mechanical ventilation (8/27, 29.6% vs. 9/10, 90.0%, P = 0.002), lower doses glucocorticoids (43.2 mg/d vs. 72.2 mg/d, P = 0.039) and had lower mortality (7/27, 25.9% vs. 8/10, 80.0%, P = 0.006) than those in the late group. In the Kaplan–Meier analysis, the survivor probability of the early group was notably higher than that of the late group (P = 0.007). Multivariate cox regression analysis showed that initiation of TMP/SMX after 7 days from admission (hazard ratio [HR]: 5.9, 95% confidence interval [CI]: 1.1–30.4; P = 0.034) and a higher level of lactate dehydrogenase (LDH; HR: 6.0, 95% CI: 1.1–31.8; P = 0.035) were associated with 90-day mortality in patients with rheumatic disease complicated by PJP. Conclusion Patients with rheumatic disease complicated by PJP had poor prognoses, with mortality rates as high as 40.5%. TMP/SMX initiation after 7 days from initial symptoms and a higher level of serum LDH were significantly associated with increased 90-day mortality.

Abstract Background More than 60% of cancer cases occur in older adults, and many are treated with oral anticancer agents. Yet, the treatment tolerability in older adults has not been fully understood due to their underrepresentation in oncology clinical trials, creating challenges for treatment decision-making and symptom management. The objective of this study was to investigate the tolerance of capecitabine, an example of oral chemotherapy, among older adults with cancer and explore factors associated with capecitabine-related side effects and treatment changes, to enhance supportive care. Methods A secondary analysis used combined data from electronic health records and a pilot study of patient-reported outcomes, with a total of 97 adult patients taking capecitabine during 2016–2017, including older adult patients aged 65 years or older (n = 43). The data extracted included patient socio-demographics, capecitabine information, side effects, and capecitabine treatment changes (dose reductions and dose interruptions). Bivariate correlations, negative binomial regression, and multiple linear regression were conducted for data analysis. Results Older adults were more likely to experience fatigue (86% vs. 51%, p = .001) and experienced more severe fatigue (β = 0.44, p = 0.03) and hand-foot syndrome (HFS) (β = 1.15, p = 0.004) than younger adults. The severity of fatigue and HFS were associated with the number of outpatient medications (β = 0.06, p = 0.006) and the duration of treatment (β = 0.50, p = 0.009), respectively. Correlations among side effects presented different patterns between younger and older adults. Although more older adults experienced dose reductions (21% vs. 13%) and dose interruptions (33% vs. 28%) than younger adults, the differences were not statistically different. Female sex, breast cancer diagnosis, capecitabine monotherapy, and severe HFS were found to be associated with dose reductions (p-values

Objective To explore the role of leptin in the onset and development of obesity-associated hypertension. Subjects and Methods A case-control study that had finished recruiting 153 subjects divided as four characteristic groups. Leptin serum levels were tested by ELISA in these subjects among these four characteristic Chinese adult physical examination groups. Waist circumference (WC), body mass index (BMI), systolic blood pressure (SB), diastolic blood pressure (DB), and other clinical laboratory data were collected. Analyzation of correlations between the research index and differences between groups was done by SPSS. Results Serum leptin levels statistically significantly positively correlated with BMI and WC, and negatively with the HDLC (high-density lipoprotein cholesterol), even after adjustment for age and gender. There was no significant difference in the serum leptin levels between the normal healthy group (NH group) and the newly diagnosed untreated just-hypertension group (JH group). And the same is between the newly diagnosed untreated obesity-hypertension group (OH group) and the newly diagnosed untreated just-obesity group (JO group). Multiple linear regression analysis indicated BMI and gender as significant independent correlates of serum leptin. Conclusions These results show leptin may not be essential but play an additive effect in the development of obesity-associated hypertension. Leptin may only play an additive effect role in the intricate interwoven network of regulators contributing to the development of hypertension in obese patients.